Alzheimer's disease (AD) involves abnormal metabolism of beta-amyloid and destruction of neurons and synapses. Since the ultimate goal of therapeutic strategies for AD is to protect neurons, we screened a variety of generic drugs for neuroprotective effect using cell culture and animals models of AD immune pathology. One widely used generic drug with anti-inflammatory properties was found to be highly neuroprotective in cell culture and animal models during pre-clinical testing. Although the same drug showed some benefit, the level of effect was not sufficient. For this reason, a more potent form of this generic drug was sought. This SBIR proposal seeks to develop drugs with neuroprotective effects in preclinical models for AD. Lead agents found to highly potent neuroprotectants in vitro will be assessed for disease-modifying effects in two in vivo assays. If the drug discovery program is successful, this project will move a class of potent neuron-protecting compounds forward to full pre-clinical development as therapeutics for disease modification of AD pathology.